ACTH stimulation tests and plasma dehydroepiandrosterone sulfate levels in women with hirsutism

Article Abstract:

Hirsutism is a clinical outcome of increased levels of male sex hormones, or androgens, in women. A number of distinct metabolic abnormalities may all produce this common symptom, and it is important to distinguish the precise cause, since the proper treatment varies depending on the source of the male hormones. Such hormones may come from the adrenal gland or the ovaries, or they may result from the conversion in local tissues of weak male hormones such as dehydroepiandrosterone (DHEA) into more potent hormones. For this reason DHEA is commonly measured in hirsute women to distinguish the cause of the hormonal imbalance. Also used in the testing of hirsute women is administration of adrenocorticotropic hormone (ACTH); the effects of ACTH may provide a clue if a deficiency of an enzyme in the steroid synthesis pathway is contributing to the problem. Both the measurement of DHEA and the ACTH stimulation test were used in the evaluation of 31 women referred for hirsutism, as well as in 22 normal control patients, to determine not only the relative frequency of the different causes of hirsutism in women, but also the effectiveness of the tests in making the determination. Of the 31 patients, 13 had an apparent deficiency of the enzyme 3-beta-hydroxy-delta-5-steroid dehydrogenase, five a deficiency of 21-hydroxylase, and one a deficiency in 11-beta-hydroxylase. Twelve patients had no signs of enzymatic activity resulting from the ACTH stimulation test. Several important observations may be made about this data. First, 19 of 31 patients, or 61 percent, had evidence of abnormal production of steroids in the adrenal gland, which suggests that such defects may be more common than previously thought. Another key observation is that the basal levels of several hormones and the levels of DHEA were of no value in predicting the defect. In particular, 6 of 11 patients with elevated DHEA were found to have no evidence of impaired steroidogenesis. Conversely, 13 patients with abnormal steroidogenesis were found to have normal DHEA. These results indicate that the measurement of DHEA levels might not only fail to identify an enzymatic defect, but might also provide misleading evidence of an adrenal defect where none is present. The ACTH stimulation test seems to be the diagnostic test of choice for hirsutism in women. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Secondary biosynthetic defects in women with late-onset congenital adrenal hyperplasia

Article Abstract:

An excess of male sex hormones has serious consequences for the developing female fetus. But late-onset, or non-classic, adrenal hyperplasia results in relatively more mild symptoms such as hirsutism (hairiness), menstrual abnormalities, and infertility. Abnormalities in adrenal steroidogenesis, or the synthesis of steroid hormones, are often not apparent if normal levels of circulating steroid hormones are measured, but become apparent if measurements are made after stimulation with the adrenocorticotrophic hormone, or ACTH. Such measurements were made in 170 Israeli Jewish women with clinical symptoms to determine the relative frequency of adrenal hyperplasia. Sixty-nine percent of these women showed no evidence of adrenal hyperplasia. Twelve percent had a defect in the enzyme 3-beta-hydroxy-delta-5-steroid dehydrogenase, 10 percent a defect in 21-hydroxylase, and 8 percent a defect in 11-beta-hydroxylase. The results indicate that late-onset adrenal hyperplasia is a common cause of hirsutism, otherwise unexplained infertility, and menstrual disorders in women. It was also found that many of the women appeared to have other defects in addition to the primary defect. For example, all 14 women who were homozygous for a deficient 21-hydroxylase activity were also partially deficient for 11-beta-hydroxylase. Although other explanations are possible, it seems most plausible that the elevation of androgens that develops over time due to the primary 21-hydroxylase deficiency may alter the regulation of 11-beta-hydroxylase and perhaps other enzymes and produce secondary deficiencies as well. (Consumer Summary produced by Reliance Medical Information, Inc.)

Infertility, Menstruation disorders

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